Association of smoking cigarettes, age, and sex with serum concentrations of olanzapine in patients with schizophrenia.

Mihovil Horvat, Mate Kadija, Andrijana Ščavničar, Maja Živković, Marina Šagud, Mila Lovrić
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Abstract

Introduction: Olanzapine is an atypical antipsychotic drug which is effective in the treatment of schizophrenia. Cigarette smoking, age, and sex could be related to the pharmacokinetics and serum concentrations of olanzapine in patients with schizophrenia. The aim of the study was to examine whether there was a significant difference in the serum olanzapine concentrations with regard to the mentioned factors.

Materials and methods: A total of 58 outpatients with schizophrenia (37 smokers, 42 men, 35 older than 40 years) participated in the study. Blood was sampled in serum tubes just before taking the next dose of olanzapine. Olanzapine was extracted by liquid-liquid extraction and was measured by an in-house high-performance liquid chromatography method on Shimadzu Prominence HPLC System with diode array detector SPD-M20A (Shimadzu, Kyoto, Japan). The results were expressed as the ratio of concentration to the daily dose of olanzapine (C/D). Non-parametric statistical tests were used to analyse differences between variables.

Results: The median C/D of olanzapine (interquartile range) in smokers was 6.0 (3.4-10.2) nmol/L/mg and in non-smokers 10.1 (5.9-17.6) nmol/L/mg; P = 0.007. The median C/D of olanzapine in patients younger than 40 years was 5.6 (4.5-10.2) nmol/L/mg and in patients older than 40 years 8.4 (5.6-13.0) nmol/L/mg; P = 0.105. The median C/D of olanzapine in male patients was 6.6 (4.6-10.4) nmol/L/mg and in female patients 9.0 (5.9-15.3) nmol/L/mg; P = 0.064.

Conclusions: The serum olanzapine concentration was significantly lower in smoking than in non-smoking patients with schizophrenia. No significant difference was demonstrated with regard to age and sex.

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精神分裂症患者吸烟、年龄和性别与血清奥氮平浓度的关系。
奥氮平是一种非典型抗精神病药物,可有效治疗精神分裂症。精神分裂症患者的吸烟、年龄和性别可能与奥氮平的药代动力学和血清浓度有关。本研究的目的是检查血清奥氮平浓度是否与上述因素存在显著差异。材料和方法:共有58名门诊精神分裂症患者(37名吸烟者,42名男性,35名40岁以上)参与了这项研究。在服用下一剂奥氮平之前,在血清管中进行血液采样。奥氮平通过液-液萃取进行提取,并通过内部高效液相色谱法在岛津Prominence HPLC系统上使用二极管阵列检测器SPD-M20A(岛津,京都,日本)进行测量。结果表示为奥氮平的浓度与每日剂量的比率(C/D)。使用非参数统计检验来分析变量之间的差异。结果:吸烟者奥氮平的中位C/D(四分位间距)为6.0(3.4-10.2)nmol/L/mg,非吸烟者为10.1(5.9-17.6)nmol/L/min;P=0.007。40岁以下患者奥氮平的中位C/D为5.6(4.5-10.2)nmol/L/mg,40岁以上患者为8.4(5.6-13.0)nmol/L/min;P=0.105。奥氮平在男性患者中的中位C/D为6.6(4.6-10.4)nmol/L/mg,在女性患者中为9.0(5.9-15.3)nmol/L/min;P=0.064。结论:吸烟组精神分裂症患者血清奥氮平浓度明显低于非吸烟组。年龄和性别方面没有显著差异。
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